Dexamethason (DEX) treated DC display several features that establish them as candidates for specific allogeneic tolerance induction. We report the results of in vitro studies of polarization of the alloimmune T cell response with two types of differentially modulated human DC. Both DEX treated DC triggered by LPS for 6 h (DEX6-DC) and DEX treated DC triggered by LPS for 48 h (DEX48-DC) acquired low levels of costimulatory, adhesion, and MHC class II molecules compared with mature DC (mDC). In contrast to mDC, both DEX6-DC and DEX48-DC did not produce any IL-12. DEX6-DC were able to produce significant amounts of IL-10 whereas DEX48-DC did not actively produce IL-10. Conversely, the induction of IL-10 producing cells was significantly increased when PBL were stimulated with DEX48-DC compared with DEX6-DC. Both stimulation of PBL with DEX6-DC and DEX48-DC led to the induction of cell populations able to suppress the proliferative alloimmune response of primed T cells in a cell-cell contact independent and antigen-nonspecific manner. Tregs obtained after stimulation with DEX48-DC were also able to inhibit the IFN-gamma production of the effector cells and this effect could be blocked by anti-IL-10. Tregs induced by DEX6-DC produced similar amounts of IL-10, yet were not able to inhibit IFN-gamma production of the effector T cells, indicating a different mechanism. In summary, we show that differential modulation of DC results in the induction of different populations of regulatory T cells.